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Title: Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.
Austin Authors: Loveland, Bruce E;Zhao, Anne;White, Shane C;Gan, Hui K ;Hamilton, Kate ;Xing, Pei-Xiang;Pietersz, Geoffrey A;Apostolopoulos, Vasso;Vaughan, Hilary A;Karanikas, Vaios;Kyriakou, Peter;McKenzie, Ian F C;Mitchell, Paul L R 
Affiliation: Austin Research Institute, and Medical Oncology Unit, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia
Issue Date: 1-Feb-2006
Publication information: Clinical Cancer Research; 12(3 Pt 1): 869-77
Abstract: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy.Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy.Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment.Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.
DOI: 10.1158/1078-0432.CCR-05-1574
Journal: Clinical Cancer Research
Type: Journal Article
Subjects: Adenocarcinoma.immunology.therapy
Antigens, Neoplasm
Cancer Vaccines.administration & dosage.immunology.toxicity
Dendritic Cells.immunology.transplantation
Dose-Response Relationship, Immunologic
Enzyme-Linked Immunosorbent Assay
Immunization Schedule
Mannans.administration & dosage.immunology.toxicity
Middle Aged
Mucins.administration & dosage.immunology
Recombinant Fusion Proteins.administration & dosage.immunology
Treatment Outcome
Appears in Collections:Journal articles

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